CEAM1_HUMAN
ID CEAM1_HUMAN Reviewed; 526 AA.
AC P13688; A6NE38; A8MY49; O60430; Q069I7; Q13854; Q13857; Q13858; Q13859;
AC Q13860; Q15600; Q15601; Q16170; Q5UB49; Q7KYP5; Q96CA7; Q9UQV9;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 1 {ECO:0000303|Ref.8};
DE AltName: Full=Biliary glycoprotein 1 {ECO:0000303|PubMed:7628460};
DE Short=BGP-1;
DE AltName: CD_antigen=CD66a;
DE Flags: Precursor;
GN Name=CEACAM1 {ECO:0000312|HGNC:HGNC:1814};
GN Synonyms=BGP {ECO:0000303|Ref.5}, BGP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6 AND 8).
RX PubMed=2537311; DOI=10.1083/jcb.108.2.267;
RA Barnett T.R., Kretschmer A., Austen D.A., Goebel S.J., Hart J.T.,
RA Elting J.J., Kamarck M.E.;
RT "Carcinoembryonic antigens: alternative splicing accounts for the multiple
RT mRNAs that code for novel members of the carcinoembryonic antigen family.";
RL J. Cell Biol. 108:267-276(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP PYROGLUTAMATE FORMATION AT GLN-35.
RX PubMed=2457922; DOI=10.1073/pnas.85.18.6959;
RA Hinoda Y., Neumaier M., Hefta S.A., Drzeniek Z., Wagener C., Shively L.,
RA Hefta L.J.F., Shively J.E., Paxton R.J.;
RT "Molecular cloning of a cDNA coding biliary glycoprotein I: primary
RT structure of a glycoprotein immunologically crossreactive with
RT carcinoembryonic antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:6959-6963(1988).
RN [3]
RP ERRATUM OF PUBMED:2457922, AND SEQUENCE REVISION.
RA Hinoda Y., Neumaier M., Hefta S.A., Drzeniek Z., Wagener C., Shively L.,
RA Hefta L.J.F., Shively J.E., Paxton R.J.;
RL Proc. Natl. Acad. Sci. U.S.A. 86:1668-1668(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RC TISSUE=Leukocyte;
RX PubMed=2025273; DOI=10.1016/s0006-291x(05)80223-2;
RA Kuroki M., Arakawa F., Matsuo Y., Oikawa S., Nakazato H., Matsuoka Y.;
RT "Three novel molecular forms of biliary glycoprotein deduced from cDNA
RT clones from a human leukocyte library.";
RL Biochem. Biophys. Res. Commun. 176:578-585(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Monocyte;
RA Kuroki M., Matsuo Y., Misumi Y., Oikawa S., Matsuoka Y.;
RT "A new isoform of human biliary glycoprotein (BGP) containing a domain
RT encoded by an Alu-like sequence.";
RL Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 293-494 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA] OF 293-458 (ISOFORM 9),
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 293-458, AND GLYCOSYLATION.
RX PubMed=8423792; DOI=10.1128/mcb.13.2.1273-1282.1993;
RA Barnett T.R., Drake L., Pickle W. II;
RT "Human biliary glycoprotein gene: characterization of a family of novel
RT alternatively spliced RNAs and their expressed proteins.";
RL Mol. Cell. Biol. 13:1273-1282(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), AND SUBCELLULAR LOCATION.
RC TISSUE=Colon adenocarcinoma;
RX PubMed=8018919;
RA Watt S.M., Fawcett J., Murdoch S.J., Teixeira A.M., Gschmeissner S.E.,
RA Hajibagheri N.M., Simmons D.L.;
RT "CD66 identifies the biliary glycoprotein (BGP) adhesion molecule: cloning,
RT expression, and adhesion functions of the BGPc splice variant.";
RL Blood 84:200-210(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11).
RA Long S., Phillips A., Ma H., Paoni N.F., Wong-Staal F., Fan W.;
RT "Isolation of the cDNA encoding a putative carcinoembryonic antigen-related
RT cell adhesion molecule 1 short form 3 (CEACAM1-3S).";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-35; VAL-83; HIS-123 AND
RP ARG-376.
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21, AND DISEASE.
RX PubMed=8055923; DOI=10.1111/j.1432-1033.1994.tb19022.x;
RA Hauck W., Nedellec P., Turbide C., Stanners C.P., Barnett T.R.,
RA Beauchemin N.;
RT "Transcriptional control of the human biliary glycoprotein gene, a CEA gene
RT family member down-regulated in colorectal carcinomas.";
RL Eur. J. Biochem. 223:529-541(1994).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RX PubMed=7628460; DOI=10.1111/j.1432-1033.1995.tb20676.x;
RA Nedellec P., Turbide C., Beauchemin N.;
RT "Characterization and transcriptional activity of the mouse biliary
RT glycoprotein 1 gene, a carcinoembryonic antigen-related gene.";
RL Eur. J. Biochem. 231:104-114(1995).
RN [15]
RP INTERACTION WITH SRC, AND PHOSPHORYLATION AT TYR-493 AND TYR-520 BY SRC.
RX PubMed=7478590;
RA Bruemmer J., Neumaier M., Goepfert C., Wagener C.;
RT "Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion
RT molecule of the carcinoembryonic antigen family downregulated in colorectal
RT carcinomas.";
RL Oncogene 11:1649-1655(1995).
RN [16]
RP NOMENCLATURE OF ALTERNATIVE SPLICING ISOFORMS.
RX PubMed=11501563; DOI=10.1006/excr.1999.4610;
RA Beauchemin N., Draber P., Dveksler G., Gold P., Gray-Owen S., Grunert F.,
RA Hammarstrom S., Holmes K.V., Karlsson A., Kuroki M., Lin S.H., Lucka L.,
RA Najjar S.M., Neumaier M., Obrink B., Shively J.E., Skubitz K.M.,
RA Stanners C.P., Thomas P., Thompson J.A., Virji M., von Kleist S.,
RA Wagener C., Watt S., Zimmermann W.;
RT "Redefined nomenclature for members of the carcinoembryonic antigen
RT family.";
RL Exp. Cell Res. 252:243-249(1999).
RN [17]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10436421; DOI=10.1159/000030075;
RA Fraengsmyr L., Baranov V., Hammarstroem S.;
RT "Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2,
RT selectively expressed in the normal human colonic epithelium, are integral
RT components of the fuzzy coat.";
RL Tumor Biol. 20:277-292(1999).
RN [18]
RP INTERACTION WITH PXN.
RX PubMed=11035932; DOI=10.1006/excr.2000.5026;
RA Ebrahimnejad A., Flayeh R., Unteregger G., Wagener C., Bruemmer J.;
RT "Cell adhesion molecule CEACAM1 associates with paxillin in granulocytes
RT and epithelial and endothelial cells.";
RL Exp. Cell Res. 260:365-373(2000).
RN [19]
RP TISSUE SPECIFICITY, AND INTERACTION WITH CEACAM8.
RX PubMed=11994468; DOI=10.4049/jimmunol.168.10.5139;
RA Singer B.B., Scheffrahn I., Heymann R., Sigmundsson K., Kammerer R.,
RA Obrink B.;
RT "Carcinoembryonic antigen-related cell adhesion molecule 1 expression and
RT signaling in human, mouse, and rat leukocytes: evidence for replacement of
RT the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked
RT proteins in human leukocytes.";
RL J. Immunol. 168:5139-5146(2002).
RN [20]
RP INTERACTION WITH ANXA2, SUBCELLULAR LOCATION, MUTAGENESIS (ISOFORM 8),
RP MUTAGENESIS OF THR-457, COMPONENT OF AIIT COMPLEX, AND PHOSPHORYLATION
RP (ISOFORM 8).
RX PubMed=14522961; DOI=10.1074/jbc.m309115200;
RA Kirshner J., Schumann D., Shively J.E.;
RT "CEACAM1, a cell-cell adhesion molecule, directly associates with annexin
RT II in a three-dimensional model of mammary morphogenesis.";
RL J. Biol. Chem. 278:50338-50345(2003).
RN [21]
RP PHOSPHORYLATION BY EGFR, AND INTERACTION WITH EGFR.
RX PubMed=15467833; DOI=10.1172/jci200421786;
RA Abou-Rjaily G.A., Lee S.J., May D., Al-Share Q.Y., Deangelis A.M.,
RA Ruch R.J., Neumaier M., Kalthoff H., Lin S.H., Najjar S.M.;
RT "CEACAM1 modulates epidermal growth factor receptor--mediated cell
RT proliferation.";
RL J. Clin. Invest. 114:944-952(2004).
RN [22]
RP INTERACTION WITH CD209.
RX PubMed=16246332; DOI=10.1016/j.febslet.2005.09.089;
RA van Gisbergen K.P., Ludwig I.S., Geijtenbeek T.B., van Kooyk Y.;
RT "Interactions of DC-SIGN with Mac-1 and CEACAM1 regulate contact between
RT dendritic cells and neutrophils.";
RL FEBS Lett. 579:6159-6168(2005).
RN [23]
RP INTERACTION WITH FLNA, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16291724; DOI=10.1242/jcs.02660;
RA Klaile E., Mueller M.M., Kannicht C., Singer B.B., Lucka L.;
RT "CEACAM1 functionally interacts with filamin A and exerts a dual role in
RT the regulation of cell migration.";
RL J. Cell Sci. 118:5513-5524(2005).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-104 AND ASN-111.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [25]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-493 AND
RP TYR-520 BY LCK, INTERACTION WITH LCK; PTPN6 AND TCR/CD3 COMPLEX, AND
RP MUTAGENESIS OF 77-ARG-GLN-78; TYR-493 AND TYR-520.
RX PubMed=18424730; DOI=10.4049/jimmunol.180.9.6085;
RA Chen Z., Chen L., Qiao S.W., Nagaishi T., Blumberg R.S.;
RT "Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits
RT proximal TCR signaling by targeting ZAP-70.";
RL J. Immunol. 180:6085-6093(2008).
RN [26]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-152; ASN-208; ASN-224; ASN-363;
RP ASN-378 AND ASN-405.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP FUNCTION, AND INTERACTION WITH KLRK1 AND PTPN6.
RX PubMed=23696226; DOI=10.1002/eji.201242676;
RA Hosomi S., Chen Z., Baker K., Chen L., Huang Y.H., Olszak T., Zeissig S.,
RA Wang J.H., Mandelboim O., Beauchemin N., Lanier L.L., Blumberg R.S.;
RT "CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function
RT and signaling.";
RL Eur. J. Immunol. 43:2473-2483(2013).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP INTERACTION WITH HAVCR2, MUTAGENESIS OF ASN-76 AND GLY-81, AND FUNCTION.
RX PubMed=25363763; DOI=10.1038/nature13848;
RA Huang Y.H., Zhu C., Kondo Y., Anderson A.C., Gandhi A., Russell A.,
RA Dougan S.K., Petersen B.S., Melum E., Pertel T., Clayton K.L., Raab M.,
RA Chen Q., Beauchemin N., Yazaki P.J., Pyzik M., Ostrowski M.A.,
RA Glickman J.N., Rudd C.E., Ploegh H.L., Franke A., Petsko G.A.,
RA Kuchroo V.K., Blumberg R.S.;
RT "CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.";
RL Nature 517:386-390(2015).
RN [31]
RP SUBUNIT.
RX PubMed=26483485; DOI=10.1073/pnas.1509511112;
RA Bonsor D.A., Gunther S., Beadenkopf R., Beckett D., Sundberg E.J.;
RT "Diverse oligomeric states of CEACAM IgV domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:13561-13566(2015).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 34-141.
RX PubMed=16929097; DOI=10.1107/s0907444906020737;
RA Fedarovich A., Tomberg J., Nicholas R.A., Davies C.;
RT "Structure of the N-terminal domain of human CEACAM1: binding target of the
RT opacity proteins during invasion of Neisseria meningitidis and N.
RT gonorrhoeae.";
RL Acta Crystallogr. D 62:971-979(2006).
CC -!- FUNCTION: [Isoform 1]: Cell adhesion protein that mediates homophilic
CC cell adhesion in a calcium-independent manner (By similarity). Plays a
CC role as coinhibitory receptor in immune response, insulin action and
CC functions also as an activator during angiogenesis (PubMed:18424730,
CC PubMed:23696226, PubMed:25363763). Its coinhibitory receptor function
CC is phosphorylation- and PTPN6 -dependent, which in turn, suppress
CC signal transduction of associated receptors by dephosphorylation of
CC their downstream effectors. Plays a role in immune response, of T
CC cells, natural killer (NK) and neutrophils (PubMed:18424730,
CC PubMed:23696226). Upon TCR/CD3 complex stimulation, inhibits TCR-
CC mediated cytotoxicity by blocking granule exocytosis by mediating
CC homophilic binding to adjacent cells, allowing interaction with and
CC phosphorylation by LCK and interaction with the TCR/CD3 complex which
CC recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70
CC (PubMed:18424730). Also inhibits T cell proliferation and cytokine
CC production through inhibition of JNK cascade and plays a crucial role
CC in regulating autoimmunity and anti-tumor immunity by inhibiting T cell
CC through its interaction with HAVCR2 (PubMed:25363763). Upon natural
CC killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of
CC CEACAM1-bearing tumor cells by trans-homophilic interactions with
CC CEACAM1 on the target cell and lead to cis-interaction between CEACAM1
CC and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation
CC (PubMed:23696226). Upon neutrophils activation negatively regulates
CC IL1B production by recruiting PTPN6 to a SYK-TLR4-CEACAM1 complex, that
CC dephosphorylates SYK, reducing the production of reactive oxygen
CC species (ROS) and lysosome disruption, which in turn, reduces the
CC activity of the inflammasome. Down-regulates neutrophil production by
CC acting as a coinhibitory receptor for CSF3R by down-regulating the
CC CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates
CC CSF3R (By similarity). Also regulates insulin action by promoting INS
CC clearance and regulating lipogenesis in liver through regulating
CC insulin signaling (By similarity). Upon INS stimulation, undergoes
CC phosphorylation by INSR leading to INS clearance by increasing
CC receptor-mediated insulin endocytosis. This inernalization promotes
CC interaction with FASN leading to receptor-mediated insulin degradation
CC and to reduction of FASN activity leading to negative regulation of
CC fatty acid synthesis. INSR-mediated phosphorylation also provokes a
CC down-regulation of cell proliferation through SHC1 interaction
CC resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and
CC phosphatidylinositol 3-kinase pathways (By similarity). Functions as
CC activator in angiogenesis by promoting blood vessel remodeling through
CC endothelial cell differentiation and migration and in arteriogenesis by
CC increasing the number of collateral arteries and collateral vessel
CC calibers after ischemia. Also regulates vascular permeability through
CC the VEGFR2 signaling pathway resulting in control of nitric oxide
CC production (By similarity). Down-regulates cell growth in response to
CC EGF through its interaction with SHC1 that mediates interaction with
CC EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-
CC MAPK1/ERK2 pathway (By similarity). Negatively regulates platelet
CC aggregation by decreasing platelet adhesion on type I collagen through
CC the GPVI-FcRgamma complex (By similarity). Inhibits cell migration and
CC cell scattering through interaction with FLNA; interfers with the
CC interaction of FLNA with RALA (PubMed:16291724). Mediates bile acid
CC transport activity in a phosphorylation dependent manner (By
CC similarity). Negatively regulates osteoclastogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809,
CC ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730,
CC ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763}.
CC -!- FUNCTION: [Isoform 8]: Cell adhesion protein that mediates homophilic
CC cell adhesion in a calcium-independent manner (By similarity). Promotes
CC populations of T cells regulating IgA production and secretion
CC associated with control of the commensal microbiota and resistance to
CC enteropathogens (By similarity). {ECO:0000250|UniProtKB:P16573,
CC ECO:0000250|UniProtKB:P31809}.
CC -!- SUBUNIT: Monomer. Oligomer. Heterodimer. Homodimer (PubMed:26483485).
CC Cis-dimer/oligomer (via Ig-like C2-type and/or via cytoplasmic
CC domains); induced by trans-homophilic cell adhesion through an
CC allosteric mechanism transmitted by the Ig-like V-type domain, and is
CC regulated by intracellular calcium and calmodulin. Interacts (via
CC cytoplasmic domain) with calmodulin in a calcium dependent manner;
CC reduces homophilic cell adhesion through dissociation of dimer (By
CC similarity). Isoform 1 interacts (via cytoplasmic domain) with PTPN11
CC (preferentially) and PTPN6; cis-homodimer form is preferred; this
CC interaction is decreased by formation of Isoform 1 /Isoform 8 cis-
CC heterodimers and is dependent on the monomer/dimer equilibrium; this
CC interaction is phosphorylation-dependent (PubMed:23696226). Isoform 1
CC interacts with LYN (By similarity). Isoform 1 interacts (via
CC cytoplasmic domain) with SRC (via SH2 domain); this interaction is
CC regulated by trans-homophilic cell adhesion (PubMed:7478590). Isoform 1
CC interacts (via cytoplasmic domain) with LCK; mediates phosphorylation
CC at Tyr-493 and Tyr-520 resulting in PTPN6 association. Isoform 1
CC interacts with PTPN6; this interaction is phosphorylation-dependent and
CC causes a profound decrease in TCR stimulation-induced CD247 and ZAP70
CC phosphorylation. Isoform 1 interacts with TCR/CD3 complex through TCR
CC beta chain and CD3E; colocalizes at the cell surface and upon
CC stimulation of the TCR/CD3 complex recruits PTPN6 in the TCR/CD3
CC complex, resulting in dephosphorylation of CD247 and ZAP70
CC (PubMed:18424730). Isoform 1 interacts (via cytoplasmic domain) with
CC SHC1 (via SH2 domain); SHC1 mediates interaction with INSR or EGFR in a
CC Ser-508 phosphorylation-dependent manner (By similarity). Isoform 1
CC interacts with EGFR; the interaction is indirect (PubMed:15467833).
CC Isoform 1 interacts with CSF3R; down-regulates the CSF3R-STAT3 pathway
CC through recruitment of PTPN6 that dephosphorylates CSF3R (By
CC similarity). Isoform 1 (phosphorylated form) interacts with TLR4 and
CC SYK; recruits PTPN6 that dephosphorylates SYK, reducing the production
CC of reactive oxygen species (ROS) and lysosome disruption, leading to a
CC reduction of the inflammasome activity (By similarity). Isoform 1
CC interacts with FLNA; inhibits cell migration and cell scattering by
CC interfering with the interaction of FLNA with RALA (PubMed:16291724).
CC Isoform 1 interacts (via cytoplasmic domain) with PXN; the interaction
CC is phosphotyrosyl-dependent (PubMed:11035932). Isoform 1 interacts with
CC KLRK1; recruits PTPN6 that dephosphorylates VAV1 (PubMed:23696226).
CC Isoform 1 interacts with CEACAM8 (PubMed:11994468). Isoform 1 interacts
CC with FASN; this interaction is insulin and phosphorylation-dependent;
CC reduces fatty-acid synthase activity (By similarity). Interacts (via
CC Ig-like V-type) with HAVCR2 (via Ig-like V-type); facilitates the
CC maturation and cell surface expression of HAVCR2 thereby regulating T
CC cell tolerance induction (PubMed:25363763). Isoform 8 interacts (via
CC the cytoplasmic domain) with ANXA2; this interaction is regulated by
CC phosphorylation and appears in the AIIt complex (PubMed:14522961).
CC Interacts (via Lewis X moieties) with CD209 (via C-type lectin domain);
CC this interaction is regulated by the glycosylation pattern of CEACAM1
CC on cell types and regulates contact between dendritic cells and
CC neutrophils (PubMed:16246332). {ECO:0000250|UniProtKB:P16573,
CC ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:11035932,
CC ECO:0000269|PubMed:11994468, ECO:0000269|PubMed:14522961,
CC ECO:0000269|PubMed:15467833, ECO:0000269|PubMed:16246332,
CC ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730,
CC ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763,
CC ECO:0000269|PubMed:26483485, ECO:0000269|PubMed:7478590}.
CC -!- INTERACTION:
CC P13688; Q16568: CARTPT; NbExp=3; IntAct=EBI-4314481, EBI-4314526;
CC P13688; P13688: CEACAM1; NbExp=3; IntAct=EBI-4314481, EBI-4314481;
CC P13688; P40199: CEACAM6; NbExp=2; IntAct=EBI-4314481, EBI-4314501;
CC P13688; Q8TDQ0: HAVCR2; NbExp=4; IntAct=EBI-4314481, EBI-11472922;
CC P13688; Q04883: opaD; Xeno; NbExp=2; IntAct=EBI-4314481, EBI-26495131;
CC P13688; Q04884: opaH; Xeno; NbExp=3; IntAct=EBI-4314481, EBI-26495102;
CC P13688; Q8GH87: uspa1; Xeno; NbExp=12; IntAct=EBI-4314481, EBI-7936357;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000250|UniProtKB:P16573}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P16573}. Lateral cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Basal cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Cell junction
CC {ECO:0000269|PubMed:16291724}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P16573}. Note=Canalicular domain of hepatocyte
CC plasma membranes. Found as a mixture of monomer, dimer and oligomer in
CC the plasma membrane. Occurs predominantly as cis-dimers and/or small
CC cis-oligomers in the cell junction regions. Found as dimer in the
CC solution. Predominantly localized to the lateral cell membranes.
CC {ECO:0000250|UniProtKB:P16573}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC {ECO:0000269|PubMed:2025273}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC {ECO:0000269|PubMed:2025273}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted
CC {ECO:0000269|PubMed:2025273}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 8]: Cell membrane
CC {ECO:0000269|PubMed:14522961}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P16573}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000269|PubMed:14522961}. Lateral cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Basal cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Cell junction
CC {ECO:0000269|PubMed:8018919}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P16573}. Note=Predominantly localized to the
CC lateral cell membranes. Found as a mixture of monomer, dimer and
CC oligomer in the plasma membrane. Occurs predominantly as cis-dimers
CC and/or small cis-oligomers in the cell junction regions (By
CC similarity). Co-localizes with ANXA2 in secretory vesicles and with
CC S100A10/p11 at the plasma membrane (PubMed:14522961).
CC {ECO:0000250|UniProtKB:P16573, ECO:0000269|PubMed:14522961}.
CC -!- SUBCELLULAR LOCATION: Cell projection, microvillus membrane
CC {ECO:0000250|UniProtKB:P31809}; Single-pass type I membrane protein
CC {ECO:0000305}. Apical cell membrane {ECO:0000269|PubMed:10436421};
CC Single-pass type I membrane protein {ECO:0000305}. Note=Localized to
CC the apical glycocalyx surface (PubMed:10436421). Colocalizes with
CC CEACAM20 at the apical brush border of intestinal cells.
CC {ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:10436421}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=11;
CC Name=1; Synonyms=BGPa, CEACAM1-4L {ECO:0000303|PubMed:11501563},
CC TM1-CEA;
CC IsoId=P13688-1; Sequence=Displayed;
CC Name=2; Synonyms=BGPg, CEACAM1-4C1 {ECO:0000303|PubMed:11501563};
CC IsoId=P13688-2; Sequence=VSP_002482, VSP_002483;
CC Name=3; Synonyms=BGPh, CEACAM1-3 {ECO:0000303|PubMed:11501563};
CC IsoId=P13688-3; Sequence=VSP_002478, VSP_002479;
CC Name=4; Synonyms=BGPi, CEACAM1-3C2 {ECO:0000303|PubMed:11501563};
CC IsoId=P13688-4; Sequence=VSP_002480, VSP_002481;
CC Name=5; Synonyms=BGPy, CEACAM1-3AL {ECO:0000303|PubMed:11501563};
CC IsoId=P13688-5; Sequence=VSP_009227;
CC Name=6; Synonyms=BGPb, CEACAM1-3L {ECO:0000303|PubMed:11501563},
CC TM2-CEA;
CC IsoId=P13688-6; Sequence=VSP_010938;
CC Name=7; Synonyms=BGPx, CEACAM1-1L {ECO:0000303|PubMed:11501563};
CC IsoId=P13688-7; Sequence=VSP_012222;
CC Name=8; Synonyms=BGPc, CEACAM1-4S {ECO:0000303|PubMed:11501563},
CC TM3-CEA;
CC IsoId=P13688-8; Sequence=VSP_040572, VSP_040574;
CC Name=9; Synonyms=BGPz, CEACAM1-3AS;
CC IsoId=P13688-9; Sequence=VSP_040571, VSP_040572, VSP_040574;
CC Name=10;
CC IsoId=P13688-10; Sequence=VSP_040573, VSP_040575;
CC Name=11; Synonyms=BGPd, CEACAM1-3S;
CC IsoId=P13688-11; Sequence=VSP_010938, VSP_040572, VSP_040574;
CC -!- TISSUE SPECIFICITY: Expressed in columnar epithelial cells of the colon
CC (at protein level) (PubMed:10436421). The predominant forms expressed
CC by T cells are those containing a long cytoplasmic domain
CC (PubMed:18424730). Expressed in granulocytes and lymphocytes.
CC Leukocytes only express isoforms 6 and isoform 1 (PubMed:11994468).
CC {ECO:0000269|PubMed:10436421, ECO:0000269|PubMed:11994468,
CC ECO:0000269|PubMed:18424730}.
CC -!- INDUCTION: Induced in primary T cells by activation with IL-2.
CC {ECO:0000269|PubMed:18424730}.
CC -!- DOMAIN: Ig-like V-type domain mediates trans-homophilic cell adhesion
CC through homodimerization and this active process is regulated by
CC tyrosine kinase, PTPN11 AND PTPN6. Ig-like C2-type and/or cytoplasmic
CC domains mediate cis-dimer/oligomer. {ECO:0000250|UniProtKB:P16573}.
CC -!- PTM: [Isoform 1]: Phosphorylated on serine and tyrosine (By
CC similarity). Isoform 1 is phosphorylated on tyrosine by Src family
CC kinases like SRC and LCK and by receptor like CSF3R, EGFR and INSR upon
CC stimulation (PubMed:15467833, PubMed:18424730, PubMed:7478590).
CC Phosphorylated at Ser-508; mediates activity. Phosphorylated at Tyr-
CC 493; regulates activity (By similarity). Phosphorylated at Tyr-493 by
CC EGFR and INSR upon stimulation; this phosphorylation is Ser-508-
CC phosphorylation-dependent; mediates cellular internalization; increases
CC interaction with downstream proteins like SHC1 and FASN (By
CC similarity). Phosphorylated at Tyr-493 and Tyr-520 by LCK; mediates
CC PTPN6 association and is regulated by homophilic ligation of CEACAM1 in
CC the absence of T cell activation (PubMed:18424730). Phosphorylated at
CC Tyr-520; mediates interaction with PTPN11 (By similarity).
CC {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809,
CC ECO:0000269|PubMed:15467833, ECO:0000269|PubMed:18424730,
CC ECO:0000269|PubMed:7478590}.
CC -!- PTM: [Isoform 8]: Phosphorylated on serine and threonine.
CC {ECO:0000269|PubMed:14522961}.
CC -!- MISCELLANEOUS: [Isoform 8]: Pseudophosphorylated double mutant Thr-
CC 457->Asp and Ser-459->Asp. The single mutant Ser-459->Asp mutant highly
CC binds with ANXA2. {ECO:0000269|PubMed:14522961}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA57141.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ceacam1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CEACAM1ID40044ch19q13.html";
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DR EMBL; J03858; AAA51826.1; -; mRNA.
DR EMBL; X14831; CAA32940.1; -; mRNA.
DR EMBL; X16354; CAA34404.1; -; mRNA.
DR EMBL; X16356; CAA34405.1; -; mRNA.
DR EMBL; D90311; BAA14341.1; -; mRNA.
DR EMBL; D90312; BAA14342.1; -; mRNA.
DR EMBL; D90313; BAA14343.1; -; mRNA.
DR EMBL; M69176; AAA51825.1; -; mRNA.
DR EMBL; M72238; AAA58393.1; -; mRNA.
DR EMBL; M72238; AAA58394.1; -; mRNA.
DR EMBL; M76741; AAA57141.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M76742; AAA57142.1; -; mRNA.
DR EMBL; M76743; AAA57143.1; -; mRNA.
DR EMBL; M76744; AAA57144.1; -; mRNA.
DR EMBL; S71326; AAB31183.1; -; mRNA.
DR EMBL; D12502; BAA02063.1; -; mRNA.
DR EMBL; AY766113; AAV34600.1; -; mRNA.
DR EMBL; DQ989182; ABI75349.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18433.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18434.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18435.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18436.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18437.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18438.1; -; Genomic_DNA.
DR EMBL; AC004785; AAC18439.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57137.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57140.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57141.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57143.1; -; Genomic_DNA.
DR EMBL; BC014473; AAH14473.1; -; mRNA.
DR EMBL; X67277; CAA47694.1; -; Genomic_DNA.
DR CCDS; CCDS12609.1; -. [P13688-1]
DR CCDS; CCDS46089.1; -. [P13688-8]
DR CCDS; CCDS54272.1; -. [P13688-11]
DR CCDS; CCDS54273.1; -. [P13688-6]
DR CCDS; CCDS54274.1; -. [P13688-5]
DR PIR; A32164; A32164.
DR PIR; B48078; B48078.
DR PIR; JH0394; JH0394.
DR PIR; JH0395; JH0395.
DR PIR; JH0396; JH0396.
DR RefSeq; NP_001020083.1; NM_001024912.2. [P13688-8]
DR RefSeq; NP_001171742.1; NM_001184813.1. [P13688-6]
DR RefSeq; NP_001171744.1; NM_001184815.1. [P13688-5]
DR RefSeq; NP_001171745.1; NM_001184816.1. [P13688-11]
DR RefSeq; NP_001192273.1; NM_001205344.1. [P13688-10]
DR RefSeq; NP_001703.2; NM_001712.4. [P13688-1]
DR RefSeq; XP_011525508.1; XM_011527206.1. [P13688-4]
DR PDB; 2GK2; X-ray; 2.20 A; A/B=34-141.
DR PDB; 4QXW; X-ray; 2.04 A; A/B=35-141.
DR PDB; 4WHD; X-ray; 2.50 A; A/B=34-141.
DR PDB; 5DZL; X-ray; 3.40 A; A/B/C/D=35-141.
DR PDB; 6AW2; X-ray; 2.68 A; A=34-141.
DR PDB; 6GBG; X-ray; 2.80 A; D=35-142.
DR PDB; 6GBH; X-ray; 2.59 A; B/D=35-142.
DR PDB; 6V3P; X-ray; 3.25 A; A/B=34-141.
DR PDB; 6XNO; X-ray; 1.90 A; A/B=35-141.
DR PDB; 6XNT; X-ray; 3.10 A; A/B=35-141.
DR PDB; 6XNW; X-ray; 1.90 A; A/B/C/D=35-141.
DR PDB; 6XO1; X-ray; 1.76 A; A/B=35-141.
DR PDB; 7MU8; X-ray; 1.70 A; A/B=35-141.
DR PDBsum; 2GK2; -.
DR PDBsum; 4QXW; -.
DR PDBsum; 4WHD; -.
DR PDBsum; 5DZL; -.
DR PDBsum; 6AW2; -.
DR PDBsum; 6GBG; -.
DR PDBsum; 6GBH; -.
DR PDBsum; 6V3P; -.
DR PDBsum; 6XNO; -.
DR PDBsum; 6XNT; -.
DR PDBsum; 6XNW; -.
DR PDBsum; 6XO1; -.
DR PDBsum; 7MU8; -.
DR AlphaFoldDB; P13688; -.
DR SMR; P13688; -.
DR BioGRID; 107103; 12.
DR DIP; DIP-42683N; -.
DR IntAct; P13688; 11.
DR MINT; P13688; -.
DR STRING; 9606.ENSP00000161559; -.
DR DrugBank; DB00113; Technetium Tc-99m arcitumomab.
DR GlyConnect; 1070; 14 N-Linked glycans (5 sites).
DR GlyGen; P13688; 24 sites, 13 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P13688; -.
DR PhosphoSitePlus; P13688; -.
DR BioMuta; CEACAM1; -.
DR DMDM; 399116; -.
DR CPTAC; CPTAC-1179; -.
DR EPD; P13688; -.
DR jPOST; P13688; -.
DR MassIVE; P13688; -.
DR MaxQB; P13688; -.
DR PaxDb; P13688; -.
DR PeptideAtlas; P13688; -.
DR PRIDE; P13688; -.
DR ProteomicsDB; 52961; -. [P13688-1]
DR ProteomicsDB; 52962; -. [P13688-10]
DR ProteomicsDB; 52963; -. [P13688-11]
DR ProteomicsDB; 52964; -. [P13688-2]
DR ProteomicsDB; 52965; -. [P13688-3]
DR ProteomicsDB; 52966; -. [P13688-4]
DR ProteomicsDB; 52967; -. [P13688-5]
DR ProteomicsDB; 52968; -. [P13688-6]
DR ProteomicsDB; 52969; -. [P13688-7]
DR ProteomicsDB; 52970; -. [P13688-8]
DR ProteomicsDB; 52971; -. [P13688-9]
DR TopDownProteomics; P13688-2; -. [P13688-2]
DR Antibodypedia; 3684; 983 antibodies from 44 providers.
DR DNASU; 634; -.
DR Ensembl; ENST00000161559.11; ENSP00000161559.6; ENSG00000079385.23. [P13688-1]
DR Ensembl; ENST00000352591.9; ENSP00000244291.6; ENSG00000079385.23. [P13688-6]
DR Ensembl; ENST00000358394.7; ENSP00000351165.2; ENSG00000079385.23. [P13688-5]
DR Ensembl; ENST00000403444.7; ENSP00000384709.3; ENSG00000079385.23. [P13688-8]
DR Ensembl; ENST00000403461.5; ENSP00000384083.1; ENSG00000079385.23. [P13688-11]
DR Ensembl; ENST00000599389.1; ENSP00000471918.1; ENSG00000079385.23. [P13688-9]
DR GeneID; 634; -.
DR KEGG; hsa:634; -.
DR MANE-Select; ENST00000161559.11; ENSP00000161559.6; NM_001712.5; NP_001703.2.
DR UCSC; uc002otv.3; human. [P13688-1]
DR CTD; 634; -.
DR DisGeNET; 634; -.
DR GeneCards; CEACAM1; -.
DR HGNC; HGNC:1814; CEACAM1.
DR HPA; ENSG00000079385; Tissue enhanced (intestine).
DR MIM; 109770; gene.
DR neXtProt; NX_P13688; -.
DR OpenTargets; ENSG00000079385; -.
DR PharmGKB; PA26358; -.
DR VEuPathDB; HostDB:ENSG00000079385; -.
DR eggNOG; ENOG502RXPD; Eukaryota.
DR GeneTree; ENSGT00960000186634; -.
DR HOGENOM; CLU_024555_2_0_1; -.
DR InParanoid; P13688; -.
DR OMA; WENSENY; -.
DR OrthoDB; 998214at2759; -.
DR PhylomeDB; P13688; -.
DR TreeFam; TF336859; -.
DR PathwayCommons; P13688; -.
DR Reactome; R-HSA-1566977; Fibronectin matrix formation.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P13688; -.
DR SIGNOR; P13688; -.
DR BioGRID-ORCS; 634; 17 hits in 1081 CRISPR screens.
DR EvolutionaryTrace; P13688; -.
DR GeneWiki; CEACAM1; -.
DR GenomeRNAi; 634; -.
DR Pharos; P13688; Tbio.
DR PRO; PR:P13688; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P13688; protein.
DR Bgee; ENSG00000079385; Expressed in ileal mucosa and 147 other tissues.
DR ExpressionAtlas; P13688; baseline and differential.
DR Genevisible; P13688; HS.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IPI:UniProtKB.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0031005; F:filamin binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; NAS:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; NAS:UniProtKB.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISS:UniProtKB.
DR GO; GO:0038158; P:granulocyte colony-stimulating factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; ISS:UniProtKB.
DR GO; GO:1901143; P:insulin catabolic process; ISS:UniProtKB.
DR GO; GO:0038016; P:insulin receptor internalization; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB.
DR GO; GO:0043318; P:negative regulation of cytotoxic T cell degranulation; IDA:UniProtKB.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; ISS:UniProtKB.
DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IMP:UniProtKB.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISS:UniProtKB.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0060312; P:regulation of blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0045601; P:regulation of endothelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:1903385; P:regulation of homophilic cell adhesion; ISS:UniProtKB.
DR GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome; Repeat;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..34
FT CHAIN 35..526
FT /note="Carcinoembryonic antigen-related cell adhesion
FT molecule 1"
FT /id="PRO_0000014562"
FT TOPO_DOM 35..428
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..526
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..142
FT /note="Ig-like V-type"
FT /evidence="ECO:0000250|UniProtKB:P31997"
FT DOMAIN 145..232
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 237..317
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 323..413
FT /note="Ig-like C2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 39..142
FT /note="Required for homophilic binding"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 450..462
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 452..526
FT /note="Interaction with FLNA"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 461..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..526
FT /note="Required for interaction with PTPN11 and PTPN6 and
FT for control of phosphorylation level"
FT /evidence="ECO:0000250|UniProtKB:P31809"
FT REGION 520..523
FT /note="Essential for interaction with PTPN11 and PTPN6"
FT /evidence="ECO:0000250|UniProtKB:P31809"
FT COMPBIAS 461..476
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 35
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2457922"
FT MOD_RES 493
FT /note="Phosphotyrosine; by SRC, LCK, INSR and EGFR"
FT /evidence="ECO:0000269|PubMed:18424730,
FT ECO:0000269|PubMed:7478590"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT MOD_RES 520
FT /note="Phosphotyrosine; by INSR, SRC and LCK"
FT /evidence="ECO:0000269|PubMed:18424730,
FT ECO:0000269|PubMed:7478590"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:16335952"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:16335952"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19159218"
FT DISULFID 167..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 259..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 348..396
FT /evidence="ECO:0000250|UniProtKB:P31809,
FT ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 143..416
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:8423792"
FT /id="VSP_012222"
FT VAR_SEQ 320..416
FT /note="ELSPVVAKPQIKASKTTVTGDKDSVNLTCSTNDTGISIRWFFKNQSLPSSER
FT MKLSQGNTTLSINPVKREDAGTYWCEVFNPISKNQSDPIMLNVNY -> D (in
FT isoform 6 and isoform 11)"
FT /evidence="ECO:0000303|PubMed:2537311, ECO:0000303|Ref.8"
FT /id="VSP_010938"
FT VAR_SEQ 320..321
FT /note="EL -> GK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002478"
FT VAR_SEQ 321..416
FT /note="LSPVVAKPQIKASKTTVTGDKDSVNLTCSTNDTGISIRWFFKNQSLPSSERM
FT KLSQGNTTLSINPVKREDAGTYWCEVFNPISKNQSDPIMLNVNY -> RQNLTMLPRLD
FT SNSWAQAILPSVSQSAEITD (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:8423792, ECO:0000303|Ref.5"
FT /id="VSP_009227"
FT VAR_SEQ 321..416
FT /note="LSPVVAKPQIKASKTTVTGDKDSVNLTCSTNDTGISIRWFFKNQSLPSSERM
FT KLSQGNTTLSINPVKREDAGTYWCEVFNPISKNQSDPIMLNVNY -> MAFHHVAKAGL
FT KLLSSSNPPASTSQSAKITD (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:8423792"
FT /id="VSP_040571"
FT VAR_SEQ 321..351
FT /note="LSPVVAKPQIKASKTTVTGDKDSVNLTCSTN -> SPVLGEDEAVPGQHHPQ
FT HKPCQEGGCWDVLV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002480"
FT VAR_SEQ 322..526
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002479"
FT VAR_SEQ 352..526
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002481"
FT VAR_SEQ 416..417
FT /note="YN -> CK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002482"
FT VAR_SEQ 418..526
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2025273"
FT /id="VSP_002483"
FT VAR_SEQ 459..464
FT /note="RASDQR -> SSGPLQ (in isoform 8, isoform 9 and
FT isoform 11)"
FT /evidence="ECO:0000303|PubMed:2537311,
FT ECO:0000303|PubMed:8018919, ECO:0000303|PubMed:8423792,
FT ECO:0000303|Ref.8"
FT /id="VSP_040572"
FT VAR_SEQ 460..468
FT /note="ASDQRDLTE -> TTPMTHLTR (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040573"
FT VAR_SEQ 465..526
FT /note="Missing (in isoform 8, isoform 9 and isoform 11)"
FT /evidence="ECO:0000303|PubMed:2537311,
FT ECO:0000303|PubMed:8018919, ECO:0000303|PubMed:8423792,
FT ECO:0000303|Ref.8"
FT /id="VSP_040574"
FT VAR_SEQ 469..526
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040575"
FT VARIANT 35
FT /note="Q -> K (in dbSNP:rs8111171)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_049844"
FT VARIANT 83
FT /note="A -> V (in dbSNP:rs8110904)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_049845"
FT VARIANT 123
FT /note="Q -> H (in dbSNP:rs8111468)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_049846"
FT VARIANT 376
FT /note="Q -> R (in dbSNP:rs41355544)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_049847"
FT MUTAGEN 76
FT /note="N->A: Impairs interaction with HAVCR2."
FT /evidence="ECO:0000269|PubMed:25363763"
FT MUTAGEN 77..78
FT /note="RQ->GL: Doesn't affect cell surface expression.
FT Impairs phosphorylation."
FT /evidence="ECO:0000269|PubMed:18424730"
FT MUTAGEN 81
FT /note="G->A: Impairs interaction with HAVCR2."
FT /evidence="ECO:0000269|PubMed:25363763"
FT MUTAGEN 457
FT /note="T->D: Decreases the binding to ANXA2."
FT /evidence="ECO:0000269|PubMed:14522961"
FT MUTAGEN 493
FT /note="Y->F: Impairs phosphorylation; when associated with
FT F-520."
FT /evidence="ECO:0000269|PubMed:18424730"
FT MUTAGEN 520
FT /note="Y->F: Impairs phosphorylation; when associated with
FT F-493."
FT /evidence="ECO:0000269|PubMed:18424730"
FT CONFLICT 142
FT /note="P -> H (in Ref. 6; AAA57142)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="D -> Y (in Ref. 5; BAA02063)"
FT /evidence="ECO:0000305"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 60..72
FT /evidence="ECO:0007829|PDB:6XO1"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:6XO1"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6XO1"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:6XO1"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:6XO1"
FT CONFLICT P13688-5:323
FT /note="N -> L (in Ref. 6; AAA57143)"
FT /evidence="ECO:0000305"
FT CONFLICT P13688-5:329
FT /note="R -> G (in Ref. 5; BAA02063)"
FT /evidence="ECO:0000305"
FT CONFLICT P13688-5:337
FT /note="Q -> E (in Ref. 6; AAA57143)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 526 AA; 57560 MW; CAD1B2328D069AF8 CRC64;
MGHLSAPLHR VRVPWQGLLL TASLLTFWNP PTTAQLTTES MPFNVAEGKE VLLLVHNLPQ
QLFGYSWYKG ERVDGNRQIV GYAIGTQQAT PGPANSGRET IYPNASLLIQ NVTQNDTGFY
TLQVIKSDLV NEEATGQFHV YPELPKPSIS SNNSNPVEDK DAVAFTCEPE TQDTTYLWWI
NNQSLPVSPR LQLSNGNRTL TLLSVTRNDT GPYECEIQNP VSANRSDPVT LNVTYGPDTP
TISPSDTYYR PGANLSLSCY AASNPPAQYS WLINGTFQQS TQELFIPNIT VNNSGSYTCH
ANNSVTGCNR TTVKTIIVTE LSPVVAKPQI KASKTTVTGD KDSVNLTCST NDTGISIRWF
FKNQSLPSSE RMKLSQGNTT LSINPVKRED AGTYWCEVFN PISKNQSDPI MLNVNYNALP
QENGLSPGAI AGIVIGVVAL VALIAVALAC FLHFGKTGRA SDQRDLTEHK PSVSNHTQDH
SNDPPNKMNE VTYSTLNFEA QQPTQPTSAS PSLTATEIIY SEVKKQ
